End-inspiratory pause prolongation in acute respiratory distress syndrome patients: effects on gas exchange and mechanics

Abstract

Background

End-inspiratory pause (EIP) prolongation decreases dead space-to-tidal volume ratio (Vd/Vt) and PaCO2. We do not know the physiological benefits of this approach to improve respiratory system mechanics in acute respiratory distress syndrome (ARDS) patients when mild hypercapnia is of no concern.

Methods

The investigation was conducted in an intensive care unit of a university hospital, and 13 ARDS patients were included. The study was designed in three phases. First phase, baseline measurements were taken. Second phase, the EIP was prolonged until one of the following was achieved: (1) EIP of 0.7 s; (2) intrinsic positive end-expiratory pressure [greater than or equal to]1 cmH2O; or (3) inspiratory-expiratory ratio 1:1. Third phase, the Vt was decreased (30 mL every 30 min) until PaCO2 equal to baseline was reached. FiO2, PEEP, airflow and respiratory rate were kept constant.

Results

EIP was prolonged from 0.12 ± 0.04 to 0.7 s in all patients. This decreased the Vd/Vt and PaCO2 (0.70 ± 0.07 to 0.64 ± 0.08, p < 0.001 and 54 ± 9 to 50 ± 8 mmHg, p = 0.001, respectively). In the third phase, the decrease in Vt (from 6.3 ± 0.8 to 5.6 ± 0.8 mL/Kg PBW, p < 0.001) allowed to decrease plateau pressure and driving pressure (24 ± 3 to 22 ± 3 cmH2O, p < 0.001 and 13.4 ± 3.6 to 10.9 ± 3.1 cmH2O, p < 0.001, respectively) and increased respiratory system compliance from 29 ± 9 to 32 ± 11 mL/cmH2O (p = 0.001). PaO2 did not significantly change.

Conclusions

Prolonging EIP allowed a significant decrease in Vt without changes in PaCO2 in passively ventilated ARDS patients. This produced a significant decrease in plateau pressure and driving pressure and significantly increased respiratory system compliance, which suggests less overdistension and less dynamic strain.

AguirreBermeo et al. Ann. Intensive Care (2016) 6:81 DOI 10.1186/s136130160183z

Endinspiratory pause prolongationinacute respiratory distress syndrome patients: eects ongas exchange andmechanics

Hernan AguirreBermeo1, Indalecio Morn1, Maurizio Bottiroli2, Stefano Italiano1, Francisco Jos Parrilla1, Eugenia Plazolles1, Ferran RocheCampo3 and Jordi Mancebo1*

Background

Mechanical ventilation in patients with acute respiratory distress syndrome (ARDS) must combine both low tidal volumes (Vt) and adequate positive end-expiratory pressure (PEEP) [1, 2]. However, in patients with ARDS, respiratory acidosis and high airway plateau pressures (Pplat) may limit management of ventilatory adjustments.

In particular, the functional consequences of hypercapnia

and respiratory acidosis may dier considerably depending on a patients condition, and they may involve almost any physiological function [36].

Optimization of mechanical ventilation parameters is associated with a reduction in dead space and is a useful strategy to reduce hypercapnia in ARDS patients [7]. Many other strategies have also been developed to decrease hypercapnia at the bedside, such as increases in respiratory rate [8], use of active humidiers [9] and the tracheal gas insufflation [10] or aspiration of dead space [11]. At bedside, the dead space could be calculated using the Engho modication of the Bohr equation. The use of this equation implies the use of PaCO2 as surrogate for

*Correspondence: [email protected]

1 Servei de Medicina Intensiva, Hospital de la Santa Creu i Sant Pau, Universidad Autnoma de Barcelona (UAB), Sant Quint, 89, 08041 Barcelona, SpainFull list of author information is available at the end of the article

2016 The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/

Web End =http://creativecommons.org/licenses/by/4.0/ ), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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alveolar carbon dioxide. Therefore, this equation measures a global index of efficiency of gas exchange because it takes also shunt eect into account [12].

Some authors have also shown that prolonging the end-inspiratory pause (EIP) is a feasible maneuver to achieve similar targets [13, 14]. In experimental models [15] and in ARDS patients [14, 1618], EIP prolongation has proven eective at enhancing CO2 elimination and decreasing partial pressure of carbon dioxide in arterial blood (PaCO2) and also physiological dead space (Vdphys). Prolonging EIP extends the time available for an enhanced diusion between inhaled Vt and resident alveolar gas, thus facilitating the transfer of CO2 from alveoli toward the airways [17, 18].

Although several of the physiological studies described above have reported that EIP prolongation improves gas exchange, none have investigated the potential physiological benets of this approach in terms of Vt reduction or improved respiratory system mechanics when hypercapnia is of no concern. To address this gap, the objective of our study was to ascertain whether EIP prolongation decreases PaCO2 and whether this eect can be used to decrease Vt while keeping PaCO2 constant. We hypothesized that this approach may have benecial eects on respiratory system mechanics in ARDS patients.

Methods

The study was performed in the Intensive Care Unit at Hospital de la Santa Creu i Sant Pau, Barcelona (Spain). The institutional ethics committee approved the study (Reference: 10/089), and the patients relatives gave signed informed consent.

Patients

Fourteen patients who met the criteria for ARDS [19] were included in the study. Exclusion criteria were: age <18years, pregnancy, hemodynamic or respiratory instability, and variation of more than 0.5C in body temperature in the last 12h before the study was planned [20]. One patient was excluded during the study period (see Results).

All patients were under sedation and analgesia with intravenous perfusion of midazolam and opiates. Neuromuscular blockade was used in all patients to prevent triggering of the ventilator. Careful endotracheal suctioning was performed before the protocol was started. Heated humidiers (Fisher & Paykel; MR 290 chamber and MR 850 ALU electric heater; Panmure, New Zealand) were used for airway humidication in all patients. These humidiers were placed in the inspiratory limb of the circuit in accordance with the manufacturers recommendations. The respiratory rate, FiO2, inspiratory ow

(square pattern) and PEEP were kept constant throughout the study.

Protocol

All patients were in steady state in the 60-min preceding data recording, and all of them were in a semirecumbent position. The study was performed in three consecutive 30-min phases. Measurements in the rst phase (baseline phase) were taken under the mechanical ventilation parameters set by the patients attending physician. In the second phase (EIP prolongation phase), the EIP was prolonged until one of the following parameters was reached: (1) EIP of 0.7s; (2) intrinsic positive end-expiratory pressure (PEEPi) 1 cmH2O; or (3) inspiratoryexpiratory ratio (I/E) of 1:1. We chose the EIP prolongation time (0.7s) based on ndings from a previous study by Devaquet etal. [18] in which a 20% prolongation of the inspiratory time induced a signicant decrease in PaCO2 and dead space. In the third phase (Vt reduction phase), the Vt was diminished in steps of 30mL every 30min until PaCO2 reached baseline levels.

The following data were collected at inclusion: demographic variables (age, sex, height), simplied acute physiology score II, ARDS etiology and days of mechanical ventilation.

During the last minute of each phase, we collected the following respiratory variables: peak airway pressure, Pplat, mean airway pressure, PEEPi, PEEP, driving airway pressure (Paw), Vt, dead space-to-Vt ratio (Vd/Vt), static compliance of the respiratory system (Crs) and airway resistance. At the same time, we recorded the following gas exchange variables: pH, partial pressure of arterial oxygen (PaO2), PaCO2 and end-tidal carbon dioxide concentration in the mixed expired gas (EtCO2). PEEPi was measured with a prolonged end-expiratory pause of 4s, performed using the ventilator expiratory hold button. EtCO2 was measured continuously with a CO2 mainstream sensor (General Electric Capnostat, Milwaukee, WI, USA). The mean value of the last 10 recorded EtCO2

values in each phase of the study was used for analysis.

Ventilatory settings and airway pressures were recorded directly from the ventilator monitoring system. Plateau pressure was measured during an endinspiratory pause. Dead space was calculated using the Engho modication of the Bohr equation [21]: Vd/ Vt = (PaCO2 PeCO2)/PaCO2, being PeCO2 the partial pressure of carbon dioxide in mixed expired gas.

Expired gas was measured by collecting gas for 3 min with a Douglas bag (P-34160; Warren E. Collins Inc., Boston, MA, USA) attached directly to the expiratory port of the ventilator. An automated analyzer (ABL 520; Radiometer A/S, Copenhagen, Denmark) was used to measure expired and arterial gases. Dead space data

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were expressed as physiological dead space (Vdphys in

mL), dened as the sum of instrumental, anatomic and alveolar dead space [22]. Driving pressure (cmH2O)

was calculated as Pplat-PEEP. Crs (mL/cmH2O) was calculated as Vt/[Pplat-(PEEP + PEEPi)], and airway resistance (cmH2O/L/s) was calculated as (peak airway pressure plateau pressure)/Flow. Predicted body weight (PBW) was calculated as follows: 50+0.91(height in cm-152.4) for men and 45.5+0.91(height in cm-152.4)

for women [8]. Arterial to end-tidal CO2 gradient (P(a-et) CO2) was calculated in each study phase. We used Puritan Bennett 840 (Covidien, Galway, Ireland) and Drger Evita XL (Drger Medical, Lbeck, Germany) ventilators. All the ventilators used have a compressible volume compensation system.

Statistical analysis

Data are expressed as mean standard deviation. The results were analyzed using one-way analysis of variance for repeated measures (ANOVA) with the Greenhouse Geisser correction. We performed the Kolmogorov Smirnov test to conrm normal data distribution. Since the distribution of the data was normal, we used the Students t test and the Pearson linear correlation to compare data and correlations between phases and variables, respectively. A two-tailed p value less than 0.05 was considered statistically signicant. The SPSS Statistics (version 20.0, Chicago, IL, USA) statistical software was used for statistical analysis.

Results

One of the 14 patients enrolled in the study was excluded from the analysis due to fever, tachypnea and unstable EtCO2 during the second phase of the study. The study was performed 54days after starting mechanical ventilation. Table 1 shows demographic data at admission,

ARDS etiology and baseline characteristics at study day.

Baseline EIP was 0.12 0.04 s, and it was increased to 0.70s in all patients (p<0.001). This EIP change was performed maintaining PEEPi <1cmH2O (0.20.2 to 0.5 0.4 cmH2O, p = 0.06) and without the I/E inverse ratio ventilation (1:4.7 0:1.3 to 1:1.7 0:0.4, p = <0.001). EIP prolongation decreased Vdphys and

PaCO2 signicantly with respect to basal conditions (26771 to 24465mL and 549 to 508mmHg, respectively; p < 0.001 for both comparisons). The decrease in PaCO2 levels due to EIP prolongation was correlated with the drop in Vdphys (r=0.871; p<0.001).

Individual changes in PaCO2 and in Vdphys are shown in Figs.1 and 2, respectively.

Between the rst and second phase, signicant decreases were observed in both the Vd/Vt ratio (0.700.07 to 0.640.08; p<0.001) and EtCO2 (416

to 39 6 mmHg; p = 0.006). Basal Vdphys and P(a-et) CO2 had a close correlation (r = 0.75; p = 0.003). The change in Vdphys and the change in P(a-et)CO2 between the rst and second phase also showed a close correlation (r=0.68; p=0.001).

In the third phase (EIP prolongation and Vt reduction), the Vt was signicantly reduced as compared to previous phases (6.30.8 to 5.60.8mL/Kg PBW; p<0.001).

In the third phase, as per protocol design, the PaCO2 and pH values were statistically identical to those at baseline (549 vs. 5410mmHg; p=0.90 and 7.310.07 vs.

7.310.08; p=0.90, respectively).

The Vdphys decreased progressively and signicantly

during all phases of the study (26771 to 24465 to 21658mL; p<0.001). The Vdphys and Vt at baseline were strongly correlated (r=0.946; p<0.001). Additionally, the

Vt reduction was tightly correlated with the decrease in Vdphys (r=0.894; p<0.001). Respiratory system mechanics, gas exchange, hemodynamics, and temperature data throughout the study are also given in Table2.

Discussion

The main nding of our study was that the end-inspira-tory pause prolongation allowed to decrease tidal volume while maintaining similar PaCO2 levels. Indeed, the decrease in tidal volume led to a signicant decrease in Pplat and Paw, and it also improved the respiratory system compliance.

Several studies have shown that prolongation of EIP enhances CO2 elimination and decreases dead space and

PaCO2 levels [1418]. Diusion of CO2 is time dependent, and EIP prolongation increases the time available for alveolar gas exchange [14, 23, 24]. Devaquet et al. [18] extended inspiratory time from 0.70.2 to 1.40.3s by increasing the inspiratory pause time from 0 to 20% of the total breathing cycle. They observed that this modication signicantly decreased both Vd/Vt (around 10%) and PaCO2 (around 11%). Despite these benecial eects of prolonged EIP and the direct relationship between inspiratory time and enhanced CO2 elimination [16, 18],

EIP prolongation may lead to potentially adverse eects such as PEEPi production and inversion of the I/E ratio together with increases in mean airway pressure. These eects might also provoke hyperination, thus altering cardiac performance [25, 26]. Nevertheless, Devaquet and colleagues [18] showed that EIP could be prolonged without signicantly increasing PEEPi (I/E ratio 1:1.5). Not surprisingly, and in spite of a signicant increase in EIP, we did not induce any signicant increase in PEEPi since the expiratory time was long enough to avoid air trapping at the end of a passive expiration (average expiratory time 1.70.3s). Actually (see Table2), the average product of three time constants (the time needed to

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Mean SD57 1147 1660.3 11.272.6 14.65 4188 640.58 0.1311 261 722 3

RR

(bpm)a

175M5967.758.5Pneumonia81120.7107022

252M4268.778Aspiration131850.65125720

346F3052.461Multiple Trauma71180.7126025

462F6947.955Pneumonia51310.6106025

556F2352.461.5Pneumonia31000.8126022

666M4063.272.5Pneumonia11840.5106020

757M6269.683Pneumonia11470.586017

836M2461.490Pneumonia42420.5147523

955M4966.872Pneumonia22190.6147021

1051F6043.364Sepsis122690.485021

1174F6147.962.5Sepsis12660.5106021

1243M6159.680.5Sepsis31940.7106022

1363M3083.1106Pneumonia62830.3586030

aFlow

ARDS etiologyDays ofMV

ARDSacute respiratory distress syndrome, FiO 2fraction of inspired oxygen, MVmechanical ventilation, PaO 2/FiO 2partial pressure of arterial oxygen over fraction of inspired oxygen, PBWpredicted body weight, PEEP

positive endexpiratory pressure, RRrespiratory rate, SAPS IIsimplied acute physiology score II

a These settings were kept constant throughout the study

(L/min)a

(cmH 2O)

FiO2aPEEP

PaO2/FiO2

(mmHg)

Table 1 Demographic data atadmission andbaseline characteristics ofpatients onthe study day

beforestudy

AdmissionStudy day

Measured

weight (kg)

GenderSAPS IIPBW

(kg)

(years)

PatientAge

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passively exhale 96% of inhaled tidal volume) was in our patients about 1.1s. (0.3733=1.1s), well below to the average expiratory time.

Prolongation of EIP in our patients caused a signi-cant decrease in dead space and PaCO2 levels that was similar to previously reported [1418]. When comparing

phase 1 (baseline) and phase 2 (isolated EIP prolongation), we found that the decrease in the Vd/Vt correlated well with the drop in PaCO2 (r=0.810; p<0.001). These changes observed in our patients may be explained by the increase on the time available for distribution and diffusion of inspired tidal gas within resident alveolar gas during EIP prolongation [14]. Indeed, total PEEP levels, airow, respiratory rate, tidal volume and respiratory mechanics were totally unchanged in this phase of our study [14, 27, 28].

Comparing the second (isolated EIP prolongation) and third (EIP prolongation and Vt reduction) phases, our data showed that the Vd/Vt ratio remained unchanged. However, the Vdphys, expressed in mL, decreased signicantly between phases 2 and 3. This is explained by the signicant reduction in Vt (that also provoked a decrease in Vdphys) during the third phase as compared to the previous phases, and thus Vd/Vt ratio did not change. The fact that the reduction in Vt in the third phase was accompanied by a signicant decrease in Vdphys and

Paw (with a signicant increase in compliance) suggests that some degree of overdistension might be present at baseline.

As previously described, low tidal volume ventilation in ARDS may induce hypercapnia and, secondarily, induce pulmonary artery hypertension that may impair right ventricular function [29] and eventually cause acute cor pulmonale [30]. To reduce hypercapnia in ARDS ventilated patients, active heated humidiers are often used. These devices signicantly decrease dead space, PaCO2

and ventilator mechanical load [9] without increasing airow resistance [31]. Although active humidication is recommended over heat and moisture exchangers in ARDS patients [32], two studies focussing on the eects of EIP prolongation on gas exchange [16, 17] did not describe the type of humidication used in their patients. A third study used passive or active humidication (10 and 5 patients, respectively) [18]. However, the eects on PaCO2 in all these studies [1618] were consistently the same, thus suggesting that humidication type per se does not inuence the eects of EIP on PaCO2.

Another technique used to decrease hypercapnia is to increase the respiratory rate. However, in ARDS patients, several studies have shown that a high respiratory rate led to gas trapping and induced PEEPi [33, 34]. In addition, experimental models suggested that higher respiratory rates may contribute to the development of ventilator-induced lung injury [35, 36]. Vieillard-Baron et al. [25] compared two respiratory rate strategies, 30 versus 15 breaths/min. They found that the high respiratory rate did not reduce PaCO2 levels but produced dynamic hyperination and reduced the cardiac index. In our patients, EIP prolongation was achieved with a relatively

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Table 2 Respiratory system mechanics, gas exchange andhemodynamic data duringthe study

Phase 1 (baseline)

Phase 2 (EIP prolongation)

Phase 3 (Vt reduction)

Overall p value

Intergroup dierences

EIP (s) 0.12 0.04 0.7 0 0.7 0 <0.001 a, b Ppeak (cmH2O) 38 6 38 6 35 5 <0.001 b, c

Pmean (cmH2O) 15 3 18 2 17 2 <0.001 a, b, c Pplat (cmH2O) 24 3 24 3 22 3 <0.001 b, c

PEEPi (cmH2O) 0.2 0.2 0.5 0.4 0.5 0.4 0.06Vt (mL) 378 73 378 73 336 61 <0.001 b, c

Vt (PBW; mL/Kg) 6.3 0.8 6.3 0.8 5.6 0.8 <0.001 b, c Vdphys (mL) 267 71 244 65 216 58 <0.001 a, b, c

Vd/Vt 0.70 0.07 0.64 0.08 0.64 0.08 <0.001 a, b Crs (mL/cmH2O) 29 9 29 9 32 11 0.001 b, c Paw (cmH2O) 13.6 3.6 13.4 3.6 10.9 3.1 <0.001 a, b, c

Raw (cmH2O/L/s) 14 5 13 5 13 4 0.28pH 7.31 0.07 7.34 0.09 7.31 0.08 <0.001 a, c

PaO2 (mmHg) 102 23 98 23 105 29 0.35PaCO2 (mmHg) 54 9 50 8 54 10 <0.001 a, c

EtCO2 (mmHg) 41 6 39 6 43 7 0.002 a, c P(aet)CO2 (mmHg) 13 6 12 8 12 9 0.27

MAP (mmHg) 80 12 76 9 77 12 0.08 HR (beats/min) 87 19 83 20 86 21 0.14

Temperature (C) 36.7 0.9 36.7 0.9 36.6 0.8 0.61

Data are presented as number (%) or meanSDIntergroup dierences (p<0.05): a, phase 1 versus phase 2; b, phase 1 versus phase 3; c, phase 2 versus phase 3

Crs static compliance of the respiratory system, EIP endinspiratory pause, EtCO2 endtidal carbon dioxide concentration in the expired air, FiO2 fraction of inspired oxygen, HR heart rate, MAP mean arterial pressure, PaO2 partial pressure of oxygen in arterial blood, PaCO2 partial pressure of carbon dioxide in arterial blood, PBW

predicted body weight, PEEPi intrinsic positive endexpiratory pressure, Pmean mean airway pressure, Ppeak peak airway pressure, Pplat plateau airway pressure, P(aet)CO2 arterial to endtidal CO2 gradient, Raw airway resistance, Vdphys physiological dead space, Vd/Vt dead spacetoVt ratio, Vt tidal volume, Paw driving airway pressure

high inspiratory ow rate (1 L/s), thus avoiding inverse I/E ratio. This was a safe strategy to decrease PaCO2 levels, while keeping respiratory rate constant (22breaths/ min) and not generating PEEPi.

In our study, the reduction in Vt to maintain isocapnia was modest. Should major reductions in Vt were required, then the use of invasive extracorporeal carbon dioxide removal devices had to be considered in order to avoid acute hypercapnia [37].

Studies analyzing the EIP prolongation did not describe changes in PaO2 [14, 18], except one study by Mercat etal. [16]. This latter study found a slight, but not statistically signicant, increase in PaO2 levels during EIP prolongation. This nding was not conrmed in our study. We speculate that the length of time that patients are maintained with EIP prolongation and the mean airway pressure achieved during extended EIP may have contributed to this nding. Indeed, in Mercats study [16], EIP prolongation was continued for 1h with a mean airway pressure of 21cmH2O and an I/E ratio 1.1. In contrast, in Devaquets study [18] and in our own study, EIP

prolongation was shorter (30min in both), mean airway pressure was lower (15 and 17cmH2O, respectively), and the I/E ratios achieved were 1:1.5 in Devaquets study and 1:1.7 in ours.

The main novelty of our study is that prolonging EIP allowed to reduce Vt by 11 % (from 6.3 0.8 to 5.60.8mL/kg of PBW; p<0.001), maintaining PaCO2 levels equal to baseline. These sequential ventilatory changes were accompanied by a reduction in Vdphys.

Also, when PaCO2 returned to baseline due to a reduction in Vt, we found a signicant decrease in Pplat and an increase in Crs. In addition, these changes in ventilatory mechanics were accompanied by a signicant decrease in Paw. All those ndings could be explained by a degree of baseline overination even though our initial Vt was low [38]. We further support our contention by the tight correlation between Vt and Vdphys at the onset of the study and the tight correlation between the decrease in Vt and Vdphys at the end of the study. Our patients were basally ventilated with parameters similar to those used in previous studies [1618] in terms of Vt and PEEP, and

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Vd/Vt was also similar. Moreover, in our patients, Crs was lower (29mL/cmH2O) than in Mercat and Devaquet studies (37 and 50 mL/cmH2O, respectively). Our ndings thus suggest that if PaCO2 is clinically tolerable, EIP prolongation in ARDS provides physiological benets including a small and consistent decrease in Vt which may help decrease dynamic strain [39].

In our study, a slight but not statistically signicant decrease in mean arterial pressure was observed. Such trend could have been the result of complex interactions of PaCO2 and mean airway pressure in cardiovascular system.

We think that EIP prolongation is a feasible maneuver to optimize the consequences of mechanical ventilation in ARDS patients. Physicians may consider using an EIP prolongation in the early phase of ARDS when patients often require sedation and neuromuscular blocking agents. In our study, we have eectively implemented this strategy by using active humidication, relatively high inspiratory ow rates and close monitoring of PEEPi. This bundle decreases PaCO2, which in turn will allow to further decrease Vt and the consequent lung strain when isocapnic conditions are met.

One of the limitations of our study is the relatively small number of patients, the majority with pneumonia, and the fact that the study is short term. Studies with patients with dierent ARDS etiologies and larger numbers are warranted to conrm our data. Also, we did not measure other parameters such as inammatory mediators or lung volumes. The calculation of dead space using the Engho modication of Bohr equation in patients with large shunt fractions (>2030 %) could underestimate dead space fraction [12]. In our study, we did not measure intrapulmonary shunt. However, according to the gas exchange values that we obtained, shunt fractions above 30% are unlikely. Additionally, the EIP prolongation increases the mechanical ination time and it could extend into neural expiration. Asynchronies may thus develop and cause an inadequate patientventilator interaction when the patients are not paralyzed [3941]. Our results could be dependent on our routine management of mechanical ventilation in ARDS patients, but our ndings have been consistent in all patients and we consider they could be extrapolated to other ARDS patients. Finally, the absolute decrease in tidal volume, although statistically signicant, is moderate.

Conclusions

In conclusion, our data indicate that EIP prolongation is a simple and feasible strategy to decrease dead space and PaCO2 levels. In addition, when PaCO2 levels are of no clinical concern, EIP prolongation allows us to further decrease tidal volume. This, in turn, decreases plateau

airway pressure, driving airway pressure and improves respiratory system compliance, suggesting less overdis-tension and less risk of dynamic strain and lung injury. Therefore, the use of this simple ventilator maneuver during mechanical ventilation in sedated and paralyzed ARDS patients merits consideration.

Abbreviations

ARDS: acute respiratory distress syndrome; Crs: static compliance of the respiratory system; EIP: endinspiratory pause; EtCO2: endtidal carbon dioxide concentration in the mixed expired gas; IE: inspiratoryexpiratory ratio; PaCO2: partial pressure of carbon dioxide in arterial blood; PaO2: partial pressure of arterial oxygen; PBW: predicted body weight; PeCO2: partial pressure of carbon dioxide in mixed expired gas; PEEP: positive endexpiratory pressure; PEEPi: intrinsic positive endexpiratory pressure; Pplat: plateau airway pressure; P(aet)

CO2: arterial to endtidal CO2 gradient; Vd/Vt: dead spacetoVt ratio; Vdphys: physiological dead space; Vt: tidal volume; Paw: driving airway pressure.

Authors contributions

All authors participated in the study design, data collection and analysis, manuscript writing and nal approval. All authors read and approved the nal manuscript.

Author details

1 Servei de Medicina Intensiva, Hospital de la Santa Creu i Sant Pau, Universi dad Autnoma de Barcelona (UAB), Sant Quint, 89, 08041 Barcelona, Spain.

2 Anestesia e Rianimazione 3, Ospedale Niguarda Ca Granda, Milan, Italy.

3 Servei de Medicina Intensiva, Hospital Verge de la Cinta, Tortosa, Spain.

Competing interests

The authors declare that they have no competing interests.

Received: 23 May 2016 Accepted: 11 August 2016

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